Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: PSTPIP1

Comment on list classification: Changed rating of gene from Red to Green. This gene was rated as Green in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.

Created: 14 Oct 2020, 1:42 p.m. | Last Modified: 14 Oct 2020, 1:42 p.m.

Panel Version: 2.298

The following PubMed IDs were added to entity PSTPIP1: 9212761;22161697;21532836. These publications have been associated with OMIM phenotype MIM#604416, which is listed for this entity, by the autoinflammation subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.

Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.

Panel Version: 2.208

Publications

• 9212761
• 22161697
• 21532836

Green List (high evidence)

agree with green gene

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

YES- this is covered on our targeted exome

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
PAPA syndrome; Hyperzincaemia hypercalprotectinaemia

Publications

• 26025129
• 28628471

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 4 variants identified in unrelated cases.

Created: 9 May 2018, 1:56 p.m.

Green List (high evidence)

Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): PSTPIP1 (also called C2BP1) .PanelApp HGNC gene symbol check: PSTPIP1 . IUIS Disease: Pyogenic sterile arthritis, pyoderma gangrenosum, acne (PAPA) syndrome, hyperzincemia and hypercalprotectinemia . IUIS Inheritance: AD .T cells: Normal, .B cells: N/A, .IUIS Other affected cells: Hematopoietic tissues, upregulated in activated T-cells. IUIS Associated features: Destructive arthritis, inflammatory skin rash, myositis. IUIS Major category: Autoinflammatory Disorders. IUIS Subcategory: Non-Inflammasome Related Conditions

Created: 2 Jul 2018, 10:35 a.m.

Comment on phenotypes: Added phenotypes suggested from external expert review.

Created: 13 Jun 2018, 11:36 a.m.

Comment on publications: added further publication suggested from expert review PMID:26025129

Created: 13 Jun 2018, 11:36 a.m.

This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.

Created: 20 Apr 2018, 12:25 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: PSTPIP1, PanelApp HGNC gene symbol check: PSTPIP1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Autoinflammatory disorders / Pyogenic sterile arthritis pyoderma gangrenosum and acne / Proline/serine/threonine phosphatase-interacting protein 1 deficiency (PSTPIP1)

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: PSTPIP1, GRID_Gene_Symbol: PSTPIP1, GRID_Transcript_ENS_Community submitted: ENST00000558012, GRID_Transcript_RefSeq: NM_003978.3, GRID_Transcript_ENS_used_on_Production: ENST00000558012

Created: 17 Apr 2018, 12:12 p.m.